可控分子量透明质酸的生物合成研究进展

肖森; 胡立涛; 石智诚; 王发银; 余思婷; 堵国成; 陈坚; 康振

doi:10.12211/2096-8280.2024-062

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可控分子量透明质酸的生物合成研究进展

特约评述 | 更新时间：2025-05-20

- 可控分子量透明质酸的生物合成研究进展
- Research advances in biosynthesis of hyaluronic acid with controlled molecular weights
- 合成生物学 2025年6卷第2期页码：445-460
- 作者机构：
  
  1.江南大学生物工程学院，糖化学与生物技术教育部重点实验室，江苏无锡 214122
  2.江南大学，未来食品科学中心，江苏无锡 214122
  3.江苏省产业技术研究院，江苏集萃未来食品技术研究所有限公司，江苏宜兴 214200
  4.江南大学生物工程学院，工业生物技术教育部重点实验室，江苏无锡 214122
- 作者简介：
  
  [ "肖森（2002—），男，硕士研究生。研究方向为透明质酸的生物合成与酶工程改造。 E-mail：6240201118@stu.jiangnan.edu.cn" ]
  [ "康振（1982—），男，博士，教授，博士生导师。研究方向为食品微生物合成生物学与生物制造。E-mail：zkang@jiangnan.edu.cn" ]
- 基金信息：
  
  江南大学食品科学与资源国家重点实验室研发项目(5962060204240220);国家自然科学基金(32370066);中央高校基本科研基金(JUSRP622003);无锡市产业创新研究院先导技术预研项目(XD24006)
- DOI：10.12211/2096-8280.2024-062
  中图分类号： Q815
- 收稿：2024-08-14，
  
  修回：2024-10-24，
  
  纸质出版：2025-04-30
- 稿件说明：
移动端阅览
肖森，胡立涛，石智诚，王发银，余思婷，堵国成，陈坚，康振. 可控分子量透明质酸的生物合成研究进展［J］. 合成生物学， 2025， 6（2）： 445-460

XIAO Sen， HU Litao， SHI Zhicheng， WANG Fayin， YU Siting， DU Guocheng， CHEN Jian， KANG Zhen. Research advances in biosynthesis of hyaluronic acid with controlled molecular weights［J］. Synthetic Biology Journal， 2025， 6（2）： 445-460
肖森，胡立涛，石智诚，王发银，余思婷，堵国成，陈坚，康振. 可控分子量透明质酸的生物合成研究进展［J］. 合成生物学， 2025， 6（2）： 445-460 DOI： 10.12211/2096-8280.2024-062.

XIAO Sen， HU Litao， SHI Zhicheng， WANG Fayin， YU Siting， DU Guocheng， CHEN Jian， KANG Zhen. Research advances in biosynthesis of hyaluronic acid with controlled molecular weights［J］. Synthetic Biology Journal， 2025， 6（2）： 445-460 DOI： 10.12211/2096-8280.2024-062.

摘要

透明质酸（hyaluronic acid， HA）是一种在化妆品、食品和医疗领域广泛应用的天然直链酸性黏多糖。根据分子量大小，HA可分为高、中、低三类，不同分子量的HA具有不同的功能和应用场景。随着微生物发酵技术取代传统动物组织提取法，HA工业化生产取得了巨大进步。然而，天然HA合成菌株兽疫链球菌的缺点（如潜在致病性以及难以分子改造），限制了不同分子量HA的生物合成研究。近年来，随着特定分子量HA需求的不断增长，代谢工程和合成生物技术已广泛应用于HA生物合成与分子量调控。本文首先分析了中高分子量HA合成的限制性因素，重点讨论了HA前体合成途径的基因调控及竞争支路的弱化。其次，探讨了HA合酶、前体供应和发酵条件对超高分子量HA合成的影响。最后，总结了低分子量HA的制备策略，包括物理化学法、酶法和微生物直接发酵法。还针对HA的生物合成与分子量调控面临的挑战——高分子量HA分子量不够高、中高分子量HA合成能力弱和低分子量HA分子量可控性差三方面展开系统性综述，加强对HA生物合成与分子量调控策略的理解，助力实现可控分子量HA的高效生物合成。

Abstract

Hyaluronic acid (HA)

a natural linear acidic polysaccharide composed of disaccharide units of D-glucuronic acid (D-GlcA) and

-acetylglucosamine (

-GlcNAc)

has been widely used in the cosmetic and medical fields. HAs with different molecular weights exhibit distinct biophysical properties. While high molecular weight HAs have stronger viscoelasticity and resistance to degradati

low molecular weight HAs demonstrate enhanced biological functions. Significant progress has been made for the industrial production of HAs

with the shift from traditional extraction from animal tissues to microbial fermentation. However

the use of the natural HA-producing species

Streptococcus zooepidemicus

presents challenges

such as potential pathogenicity and difficulties in molecular modifications

which limit the study on the biosynthesis of HAs with varying molecular weights. Recently

the increasing demand for specific molecular weight HAs has driven the application of metabolic engineering and synthetic biology techniques for their biosynthesis and molecular weight regulation. By identifying the key factors involved in the processes

researchers have developed various strategies to optimize the synthesis of HAs and control their molecular weights. This article first analyzes the limiting factors in the synthesis of medium and high molecular weight HAs

focusing on the genetic regulation on the synthesis pathways of HA precursors and the weakening of competitive branches. Secondly

it discusses the impact of HA synthase

precursor supply

and fermentation conditions on the synthesis of ultra-high molecular weight HAs. Finally

it summarizes the preparation strategies for low molecular weight HAs

including physical and chemical methods

enzymatic methods

and microbial direct fermentation as well. The review summarizes the latest research progress regarding challenges faced in the biosynthesis and molecular weight regulation of HAs: specifically

the insufficient molecular weight of high molecular weight HAs

the weak synthesis capability of medium molecular weight HAs

and the poor controllability of low molecular weight HAs. It provides a systematic overview on enhancing the understanding of strategies for HA biosynthesis and molecular weight regulation

aiming to facilitate the efficient biosynthesis of HAs with controlled molecular weights.

关键词

Keywords

references

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